Association of parents' physical activity and weight status with obesity and metabolic risk of their offspring / Associação do status de atividade física e peso dos pais com os indicadores de obesidade e risco metabólico dos filhos

Abstract Our aim was to analyze the joint association of parental characteristics and offspring obesity indicators with metabolic risk in adolescents. A cross-sectional study was carried out with 972 adolescents and their parents. We observed that overweight adolescents who have a normal weight mother show lower metabolic risk in comparison with their counterparts with overweight mothers. In conclusion, mother's weight status moderates the relationship between offspring' obesity indicators and metabolic risk in adolescents.

Resumo Nosso objetivo foi analisar a associação combinada entre características dos pais e indicadores de adiposidade dos filhos com o risco metabólico em adolescentes. Foi realizado estudo transversal com 972 adolescentes e seus pais. Observamos que adolescentes com sobrepeso que possuem mãe com peso normal apresentaram menor risco metabólico em comparação com seus pares com mães que apresentam sobrepeso. Concluímos que o status de peso da mãe modera a relação entre indicadores de obesidade e risco metabólico dos adolescentes.

Increased nitro-oxidative toxicity in association with metabolic syndrome, atherogenicity and insulin resistance in patients with affective disorders.

BACKGROUND: There is a strong comorbidity between mood disorders and metabolic syndrome (MetS). Increased levels of reactive oxygen and nitrogen species (RONS) and nitro-oxidative stress toxicity (NOSTOX) partially underpin this comorbidity. AIMS: To examine the associations of RONS/NOSTOX biomarkers with MetS after adjusting for the significant effects of mood disorders (major depression, and bipolar type 1 and 2), generalized anxiety disorder (GAD), tobacco use disorder (TUD), and male sex. METHODS: The study included subjects with (n=65) and without (n=107) MetS and measured levels of superoxide dismutase 1 (SOD1), lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), malondialdehyde (MDA), and advanced oxidation protein products (AOPP) and computed z unit-weighted composite scores which reflect RONS/NOSTOX. The study included 105 patients with mood disorders, 46 with GAD, and 95 with TUD. RESULTS: MetS was associated with increased levels of MDA and AOPP, independently from mood disorders, TUD, sex and GAD. Atherogenicity and insulin resistance (IR) were significantly associated with a NOSTOX composite score. Mood disorders, TUD, GAD, male sex and MetS independently contribute to increased RONS/NOSTOX. The RONS/NOSTOX profile of MetS was different from that of GAD, which showed increased SOD1 and NOx levels. TUD was accompanied by increased SOD1, LOOH and MDA, and male sex by increased LOOH and AOPP. CONCLUSIONS: MetS is characterized by increased lipid peroxidation with aldehyde formation and chlorinative stress, and atherogenicity and IR are strongly mediated by RONS/NOSTOX. Partially shared RONS/NOSTOX pathways underpin the comorbidity of MetS with mood disorders, GAD, and TUD.

Vitamin D deficiency is not associated with increased oxidative stress in chronic kidney disease pre-dialysis patients / A deficiência de vitamina D não está associada ao aumento do estresse oxidativo em pacientes renais crônicos em pré-diálise

Abstract Introduction: The progressive decline in 25-hydroxyvitamin D [25(OH)D] in chronic kidney disease (CKD) limits the kidney ability of synthesizing the vitamin. Vitamin D deficiency as defined by KDIGO (25(OH)D <20 ng/mL) is prevalent in CKD patients and associated to oxidative stress (OS). We studied a possible association between vitamin D deficiency and OS in pre-dialysis patients. Methods: A cross-sectional study with 206 CKD patients was carried out. Laboratory tests for 25(OH)D, 1,25(OH)2D, inflammatory markers, and OS were added to routine tests including creatinine, albumin, calcium, phosphorus, alkaline phosphatase, iPTH, glucose, hemoglobin, uric acid, total cholesterol, LDL, HDL, and triglycerides. Results: Vitamin D deficiency was present in 55 CKD patients and normal vitamin D levels were seen in 149 patients. There was a significant association between vitamin D and estimated glomerular filtration rate (eGRF). Homocysteine levels were best predicted by eGRF, sex, and age; high sensitivity C-reactive protein (hsCRP) by staging and BMI; nitric oxide metabolites (NOx) were increased in late disease; leptin was influenced by BMI and higher in women than man; and adiponectin levels were higher in women. Conclusions: OS biomarkers were not correlated with vitamin D deficiency but increased NOx were seen in stages 4-5 CKD patients. Even though a relatively large number of CKD patients was included and a broad number of OS and inflammatory biomarkers were used in this studied we failed to find an association between vitamin D levels and eGRF. More studies are needed to evaluate the influence of vitamin D status in OS in pre-dialysis CKD patients.

Resumo Introdução: A queda da 25-hidroxivitamina D [25 (OH) D] na doença renal crônica (DRC) limita a capacidade renal de sintetizar a vitamina. A deficiência de vitamina D, (25(OH)D<20 ng/mL), é prevalente em pacientes com DRC e associada ao estresse oxidativo (EO). Avaliamos possível associação entre a deficiência de vitamina D e EO em pacientes pré-dialíticos. Métodos: estudo transversal com 206 pacientes com DRC. Exames para 25(OH)D, 1,25(OH)2D, marcadores inflamatórios e EO foram adicionados àqueles de rotina, incluindo creatinina, albumina, cálcio, fósforo, fosfatase alcalina, iPTH, glicose, hemoglobina, ácido úrico, colesterol total , LDL, HDL e triglicerídeos. Resultados: 55 pacientes com DRC tinham deficiência de vitamina D e os 149 tinham níveis normais da vitamina. Houve uma associação significativa entre a vitamina D e a taxa estimada de filtração glomerular (TFGe). Os níveis de homocisteína foram melhor previstos pela TFGe, gênero e idade; proteína C reativa de alta sensibilidade (hsCRP) por estadiamento e IMC; os metabólitos de óxido nítrico (NOx) aumentaram na doença tardia; a leptina foi influenciada pelo IMC, e mais alta em mulheres, assim como os níveis de adiponectina. Conclusões: biomarcadores do EO não correlacionaram com a deficiência de vitamina D, mas houve aumento de NOx nos estágios 4-5 da DRC. Apesar dos grandes números de pacientes com DRC, de biomarcadores inflamatórios e EO usados neste estudo, não houve associação entre os níveis de vitamina D e a TFGe. Mais estudos são necessários para avaliar a influência do status da vitamina D no EO em pacientes com DRC em pré-diálise.

Silver serum levels in burned patients treated with silver sulfadiazine and its toxicity on inflammatory cells.

BACKGROUND: Silver sulfadiazine (SSD) has been widely used in burned patients for the prevention of local infections. To be biologically active and exert antimicrobial properties, silver needs to be present in the form of silver ions (Ag1+) that bind to negatively charged proteins, namely, the RNA and DNA in microorganisms. However, previous published studies conducted with SSD in the 1990s reported a high level of silver absorption through damaged skin and noted the potential cytotoxicity of Ag1+ to human cells. SSD toxicity, however, had been described in cell cultures using arbitrary silver concentrations. In the present study, we determined the serum silver levels in burned patients treated with SSD and, taking into account the molar Ag1+ concentrations found in these patients, we evaluated the Ag1+ toxicity effects on inflammatory cells (ROS and cytokine production) in vitro. METHODS: Twenty patients with an average burned body surface area of 27.68% were included in this study. RESULTS: Patients' Ag1+ serum levels reached up to 558 times those of the unexposed controls. Ag1+ was then added to inflammatory cells in vitro at levels up to 2000 times the level of the control, and there was no effect on the viability of the cells nor on the rate of apoptosis. We observed a decrease in reactive oxygen species production by mononuclear (MN) and polymorphonuclear (PMN) cells, as well as a substantial decrease in cytokines IL-1ß, IL-6, IL-8, IL-10, and TNF-α production by leukocytes (MN and PNM). CONCLUSION: These findings suggest that Ag1+ may contribute to negative outcomes after burns, decreasing the primary defense mechanism (respiratory burst) and altering cytokine production.

Gestational exposure to paracetamol in rats induces neurofunctional alterations in the progeny.

Paracetamol (PAR) is an over-the-counter medicine used as analgesic or antipyretic by 40-50% of the pregnant women in different countries. Epidemiologic studies have been associating maternal use of PAR with neurodevelopmental disruption and special attention has been given to its potential to increase the odds for neurodevelopmental disorders, such as attention-deficit hyperactive disorder and autism spectrum disorder. Population-based research do not allow the establishment of causal relationships because variable control is weak. We aimed to evaluate the potential of PAR to induce developmental neurotoxicity in rats. Pregnant Wistar rats were gavaged with PAR (350 mg/kg/day) or water from gestational day 6 until delivery. General toxicity endpoints included dams' body weight and food intake as well as pups' body weight until weaning. Behavioral evaluation occurred at post-natal days 10 (nest seeking test), 27 (behavioral stereotypy), 28 (three chamber sociability test and open field) and 29 (hot plate and elevated plus-maze). Moreover, lipid hidroperoxide (LOOH), reduced glutathione (GSH) and brain derived neurotrophic factor (BDNF) levels were quantified in prefrontal cortex and hippocampus of 22-days-old rats. Gestational exposure to PAR impaired nest seeking behavior, augmented apomorphine-induced behavioral stereotypy and decreased rostral grooming in the elevated plus maze. Exposed female pups presented elevated vertical exploration in the open field test. No alterations were observed in LOOH, GSH or BDNF levels in the prefrontal cortex or hippocampus. Exposure regimen did not affect general toxicity parameters or pups' behavior in the hot plate and sociability tests. These data suggest PAR as a developmental neurotoxicant. Observed alterations may be relevant for neurodevelopmental disorders.

Functional iron deficiency in patients on hemodialysis: prevalence, nutritional assessment, and biomarkers of oxidative stress and inflammation / Deficiência funcional de ferro em pacientes em hemodiálise: prevalência, avaliação nutricional e de biomarcadores de estresse oxidativo e de inflamação

Abstract Introduction: Anemic patients with chronic kidney disease (CKD) can be divided into anemic patients without or with functional iron deficiency (FID). The increase in the number of cases of hemosiderosis in patients on hemodialysis (HD) attributed to excessive intravenous iron replacement has called for the investigation of the factors involved in the genesis of FID. Objectives: This study aimed to describe the prevalence of FID in patients with CKD on HD, characterize the included individuals in terms of clinical and workup parameters, and assess their nutritional, oxidative stress, and inflammation statuses. This cross-sectional study assembled a convenience sample of 183 patients with CKD on HD treated in Southern Brazil. Patients meeting the inclusion and exclusion criteria were divided into two groups, one with anemic subjects with FID and one with anemic patients without FID. Participants answered a questionnaire probing into socio-epidemiological factors, underwent anthropometric measurements, and were tested for markers of anemia, oxidative stress, inflammation, and nutrition. Statistical analysis: The date sets were treated on software package GraphPad InStat version 3.1. Variables were tested with the Kolmogorov-Smirnov, chi-square, Student's t, and Mann-Whitney tests. Statistical significance was attributed to differences with a p < 0.05. Results: Markers of inflammation were not statistically different between the two groups. Markers of anemia and nutrition were significantly lower in patients with FID. Patients with FID were prescribed higher doses of parenteral iron (p < 0,05). Discussion: FID was associated with lower nutritional marker levels, but not to increased levels of markers of inflammation or oxidative stress, as reported in the literature. Additional studies on the subject are needed.

Resumo Introdução: A anemia na DRC pode ser dividida em anemia sem deficiência funcional de ferro e com deficiência funcional de ferro (ADFF). Diante do aumento dos casos de hemossiderose em pacientes em hemodiálise, atribuídos à reposição excessiva de ferro endovenoso, maiores conhecimentos sobre os fatores envolvidos na gênese da ADFF são importantes. Objetivos: documentar a prevalência de ADFF em renais crônicos em hemodiálise. Caracterizar clínica e laboratorialmente os portadores de ADFF em HD e avaliar o estado nutricional, estresse oxidativo e inflamatório. Estudo transversal, amostra de conveniência, envolvendo 183 renais crônicos em hemodiálise no sul do Brasil. Após aplicação dos critérios de exclusão, os pacientes foram separados em dois grupos: portadores de anemia com e sem deficiência funcional de ferro. Foram submetidos a questionário socioepidemiológico, à análise antropométrica e análise laboratorial dos marcadores de anemia, estresse oxidativo, inflamatórios e nutricionais. Análise estatística: programa GraphPad InStat versão 3.1. Foram aplicados os testes: Kolmogorov-Smirnov, qui-quadrado, t de Student e Mann-Whitney. Nível de significância adotado de 5%. Resultados: não houve diferença significativa nos marcadores inflamatórios entre os dois grupos. Houve diferença significativa nos marcadores de anemia e nutrição, significativamente menores nos pacientes com ADFF. Pacientes com ADFF receberam doses mais elevadas de ferro parenteral (p < 0,05). Discussão: ADFF esteve associada a menores valores de marcadores nutricionais, mas não esteve associada a marcadores inflamatórios ou de estresse oxidativo aumentados, como relatado na literatura. Estudos adicionais sobre o tema são necessários.

Functional iron deficiency in patients on hemodialysis: prevalence, nutritional assessment, and biomarkers of oxidative stress and inflammation.

INTRODUCTION: Anemic patients with chronic kidney disease (CKD) can be divided into anemic patients without or with functional iron deficiency (FID). The increase in the number of cases of hemosiderosis in patients on hemodialysis (HD) attributed to excessive intravenous iron replacement has called for the investigation of the factors involved in the genesis of FID. OBJECTIVES: This study aimed to describe the prevalence of FID in patients with CKD on HD, characterize the included individuals in terms of clinical and workup parameters, and assess their nutritional, oxidative stress, and inflammation statuses. This cross-sectional study assembled a convenience sample of 183 patients with CKD on HD treated in Southern Brazil. Patients meeting the inclusion and exclusion criteria were divided into two groups, one with anemic subjects with FID and one with anemic patients without FID. Participants answered a questionnaire probing into socio-epidemiological factors, underwent anthropometric measurements, and were tested for markers of anemia, oxidative stress, inflammation, and nutrition. STATISTICAL ANALYSIS: The date sets were treated on software package GraphPad InStat version 3.1. Variables were tested with the Kolmogorov-Smirnov, chi-square, Student's t, and Mann-Whitney tests. Statistical significance was attributed to differences with a p < 0.05. RESULTS: Markers of inflammation were not statistically different between the two groups. Markers of anemia and nutrition were significantly lower in patients with FID. Patients with FID were prescribed higher doses of parenteral iron (p < 0,05). DISCUSSION: FID was associated with lower nutritional marker levels, but not to increased levels of markers of inflammation or oxidative stress, as reported in the literature. Additional studies on the subject are needed.

Early Life Trauma Predicts Affective Phenomenology and the Effects are Partly Mediated by Staging Coupled with Lowered Lipid-Associated Antioxidant Defences.

Background Early life trauma (ELT) may drive mood disorder phenomenology, nitro-oxidative pathways and impairments in semantic memory. There are no data regarding the impact of ELT on affective phenomenology and whether these pathways are mediated by staging or lowered lipid-associated antioxidant defences. Methods This study examined healthy controls (n=54) and patients with affective disorders including major depression, bipolar disorder and anxiety disorders (n=118). ELT was assessed using the Child Trauma Questionnaire. In addition, we measured affective phenomenology and assayed advanced oxidation protein products; malondialdehyde, paraoxonase 1 (CMPAase) activity, high-sensitivity C-reactive protein (hsCRP), and high-density lipoprotein (HDL) cholesterol. Results ELT was associated into with increased risk for mood and comorbid anxiety disorders and a more severe phenomenology, including staging characteristics, depression and anxiety severity, suicidal behaviours, type of treatments, disabilities, body mass index, smoking behaviour and hsCRP, as well as lowered health-related quality of life, antioxidant defences and semantic memory. The number of mood episodes and CMPAase/HDL-cholesterol levels could be reliably combined into a new vulnerability staging-biomarker index, which mediates in part the effects of ELT on affective phenomenology and oxidative stress. Moreover, the effects of female sex on mood disorders and affective phenomenology are mediated by ELT. Discussion The cumulative effects of different ELT drive many aspects of affective phenomenology either directly or indirectly through effects of staging and/or lipid-associated antioxidant defences. The results show that children, especially girls, with ELT are at great risk to develop mood disorders and more severe phenotypes of affective disorders.

Generalized Anxiety Disorder (GAD) and Comorbid Major Depression with GAD Are Characterized by Enhanced Nitro-oxidative Stress, Increased Lipid Peroxidation, and Lowered Lipid-Associated Antioxidant Defenses.

Accumulating evidence shows that nitro-oxidative pathways play an important role in the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD) and maybe anxiety disorders. The current study aims to examine superoxide dismutase (SOD1), catalase, lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), malondialdehyde (MDA), glutathione (GSH), paraoxonase 1 (PON1), high-density lipoprotein cholesterol (HDL), and uric acid (UA) in participants with and without generalized anxiety disorder (GAD) co-occurring or not with BD, MDD, or tobacco use disorder. Z unit-weighted composite scores were computed as indices of nitro-oxidative stress driving lipid and protein oxidation. SOD1, LOOH, NOx, and uric acid were significantly higher and HDL and PON1 significantly lower in participants with GAD than in those without GAD. GAD was more adequately predicted by increased SOD + LOOH + NOx and lowered HDL + PON1 composite scores. Composite scores of nitro-oxidative stress coupled with aldehyde and AOPP production were significantly increased in participants with comorbid GAD + MDD as compared with all other study groups, namely MDD, GAD + BD, BD, GAD, and healthy controls. In conclusion, GAD is characterized by increased nitro-oxidative stress and lipid peroxidation and lowered lipid-associated antioxidant defenses, while increased uric acid levels in GAD may protect against aldehyde production and protein oxidation. This study suggests that increased nitro-oxidative stress and especially increased SOD1 activity, NO production, and lipid peroxidation as well as lowered HDL-cholesterol and PON1 activity could be novel drug targets for GAD especially when comorbid with MDD.

Lowered quality of life in mood disorders is associated with increased neuro-oxidative stress and basal thyroid-stimulating hormone levels and use of anticonvulsant mood stabilizers.

RATIONALE, AIMS: Major affective disorders including bipolar disorder (BD) and major depressive disorder (MDD) are associated with impaired health-related quality of life (HRQoL). Oxidative stress and subtle thyroid abnormalities may play a pathophysiological role in both disorders. Thus, the current study was performed to examine whether neuro-oxidative biomarkers and thyroid-stimulating hormone (TSH) levels could predict HRQoL in BD and MDD. METHODS: This cross-sectional study enrolled 68 BD and 37 MDD patients and 66 healthy controls. The World Health Organization (WHO) QoL-BREF scale was used to assess 4 QoL subdomains. Peripheral blood malondialdehyde (MDA), advanced oxidation protein products, paraoxonaxe/CMPAase activity, a composite index of nitro-oxidative stress, and basal TSH were measured. RESULTS: In the total WHOQoL score, 17.3% of the variance was explained by increased advanced oxidation protein products and TSH levels and lowered CMPAase activity and male gender. Physical HRQoL (14.4%) was associated with increased MDA and TSH levels and lowered CMPAase activity. Social relations HRQoL (17.4%) was predicted by higher nitro-oxidative index and TSH values, while mental and environment HRQoL were independently predicted by CMPAase activity. Finally, 73.0% of the variance in total HRQoL was explained by severity of depressive symptoms, use of anticonvulsants, lower income, early lifetime emotional neglect, MDA levels, the presence of mood disorders, and suicidal ideation. CONCLUSIONS: These data show that lowered HRQoL in major affective disorders could at least in part result from the effects of lipid peroxidation, protein oxidation, lowered antioxidant enzyme activities, and higher levels of TSH.

Effects of adjunctive N-acetylcysteine on depressive symptoms: Modulation by baseline high-sensitivity C-reactive protein.

Outcomes in a RCTs of 12 weeks of theclinical efficacy of N-acetylcysteine (NAC) as an adjunctive treatment on depression and anxiety symptoms and its effects on high-sensitivity C-reactive protein (hs-CRP) levels. A wide array of measures were made. The 17-item version of the Hamilton Depression Rating Scale (HDRS17); the Hamilton Anxiety Rating Scale (HAM-A); Sheehan Disability Scale; Quality of Life; Clinical Global Impression (CGI); anthropometrics measures; and vital signs and biochemical laboratory. There were no significant differences among the groups regarding demographic, clinical features, use of medication, metabolic syndrome and comorbidities. From baseline to week 12, individuals receiving NAC, versus placebo, had a statistically significant reduction in depressive symptoms on HDRS17 (p < 0.01) and anxiety symptoms on HAM-A (p = 0.04), but only for individuals with levels of hs-CRP > 3 mg/L at baseline. Individuals receiving NAC with baseline levels of hs-CRP > 3 mg/L, had more significant reduction in uric acid levels compared to individuals with baseline levels of hs-CRP ≤ 3 mg/L on week 12. Participants receiving placebogained significantly more weight during the 12 weeks for baseline levels of hs-CRP ≤ 3 mg/L and hs-CRP > 3 mg/L, and individuals receiving NAC in both groups did not have significant weight change during the 12 weeks. No individuals were withdrawn from the study because of adverse event. NAC group exhibited significantly greater reduction on hs-CRP levels than placebo group from baseline to week 12. TRIAL REGISTRATION: clinicaltrials.gov Identifier; NCT02252341.

Interferon-gamma in mobilized stem cells: A possible prognostic marker in early post-transplant management in multiple myeloma.

INTRODUCTION: A complex network of cytokines in the bone marrow microenvironment has been implicated as an important factor in the pathogenesis of multiple myeloma (MM). Different cytokines have been studied in MM, both in peripheral blood and/or bone marrow, but there are few data correlating cytokines in leukapheresis product with post-transplant response depth to treatment. MATERIALS AND METHODS: In a retrospective cross-sectional study, levels of tumor necrosis factor alpha (TNF-α), transforming growth factor beta-1 (TGF-ß1) and interferon gamma (IFN-γ) in peripheral hematopoietic stem cells/leukapheresis product (PHSC) of patients with MM eligible for transplantation were evaluated. Association of these cytokines with certain factors such as mobilized CD34 + cells/kg, staging, response to treatment and outcome were analyzed. RESULTS: The median baseline IFN-γ level was 826.4 pg/mL. IFN-γ levels in the leukapheresis product were significantly lower in patients who achieved complete response (CR) three months post-transplant when compared to patients with very good partial response (VGPR) (674.75 ±â€¯80.32 pg/mL versus 939.6 ±â€¯106.8 pg/mL, p = 0.02), respectively. Patients who lost depth of response at the third-month post-transplant had a median level of IFN-γ 1133, being considered "high-expressors" of IFN-γ, while those reaching improved response were called "low-expressors" (median level IFN-γ 485 pg/mL). Overall and progression-free survival did not have a statistically significant correlation with TNF-α, TGF-ß1 or IFN-γ, as well as TNF-α and TGF-ß1 levels in post-transplant response assessment. CONCLUSION: IFN-γ in PHSC seems to be an important biomarker of loss of response in MM, suggesting a role in early post-transplant therapeutic management.

Phase angle is related with inflammatory and oxidative stress biomarkers in older women.

BACKGROUND: The aim of this study was to examine the relation between phase angle (PhA) and inflammatory and oxidative stress biomarkers in older women. METHODS: One hundred and fifty-five physically independent older women participated in this study (67.7±5.7years, 27.0±4.4kg/m2). Inflammatory markers included interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and acute phase reactive protein (CRP). Oxidative stress biomarkers comprised superoxide dismutase (SOD), catalase (CAT), advanced oxidation protein products (AOPP), and total radical-trapping antioxidant potential (TRAP). A spectral bioelectrical impedance device was used to estimate resistance (R) and reactance (Xc) at frequency 50kHz, and subsequently PhA was calculated as arc-tangent (Xc/R)×180°/π. The covariates appendicular lean soft-tissue (ALST), trunk fat mass, and total body fat were determined by whole-body dual-energy X-ray absorptiometry. Linear regression analysis was conducted to further test if PhA is related with the dependent variables, after adjusting for potential covariates. RESULTS: After controlling for the potential covariates (age, trunk fat mass, ALST, and number of diseases) PhA exhibited a significant inverse relation with IL-6 (ß=-0.97; P<0.01), TNF-α (ß=-0.84; P<0.01), and CRP (ß=-0.58; P<0.01). Conversely, PhA was significantly related to CAT (ß=7.27; P<0.01), SOD (ß=10.55; P<0.01) and TRAP (ß=73.08; P<0.01). The AOPP did not demonstrate a significant correlation with PhA (P>0.05). CONCLUSION: Our findings show that PhA is a simple and relevant explanatory variable which is related inflammatory and stress oxidative markers in physically independent older women, regardless of age, number of diseases, and body composition.

Associations between severity of anxiety and clinical and biological features of major affective disorders.

Patients with major affective disorders (MAFD) with comorbid anxiety show a greater functional impairment than those without anxiety. The aim of this study is to delineate the associations between severity of anxiety in MAFD, namely bipolar disorder (BD) and major depression (MDD), and MAFD characteristics and serum high-density lipoprotein (HDL)-cholesterol levels. Recruited were 82 participants with anxiety disoders and 83 without anxiety disoders, including 101 MAFD patients and 51 healthy controls. We used the Hamilton Anxiety Rating Scale (HAM-A) to measure severity of anxiety and made the diagnoses of posttraumatic stress disorder (PTSD), obsessive compulsive disorder (OCD), panic disorder (PD), generalized anxiety disorder (GAD) and phobias. The HAM-A score is significantly predicted by higher number of depressive episodes, GAD and phobias, childhood trauma, tobacco use disorder, metabolic syndrome and lowered HDL-cholesterol. Increased HAM-A scores are, independently from severity of depression, associated with lowered quality of life, increased disabilities and suicidal ideation. Lithium treatment significantly lowers HAM-A scores. It is concluded that severity of anxiety significantly worsens the phenomenology of MAFD. Therefore, treatments of MAFD should target increased severity of anxiety and its risk factors including low HDL-cholesterol, metabolic syndrome, childhood trauma and tobacco use disorder.

Oxidative and nitrosative stress biomarkers in chronic schizophrenia.

There is evidence that the acute phase of schizophrenia (SCZ) is accompanied by specific changes in oxidative and nitrosative stress (O&NS) biomarkers. There are, however, no firm data regarding these biomarkers in chronic SCZ. Therefore, this study aimed to delineate O&NS biomarkers in patients with chronic SCZ. 125 outpatients with SCZ and 118 controls were enrolled. The markers included lipid hydroperoxides (LOOH), advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), total radical-trapping antioxidant parameter (TRAP) and paraoxonase 1 (PON-1) activity. Immune-inflammatory markers known to be altered in SCZ were also measured: leptin, IL-6, soluble TNF receptors (sTNF-Rs) and the chemokines CCL-11 and CCL-3. There were no significant associations between chronic SCZ and the O&NS markers (AOPP, NOx, LOOH) and the anti-oxidants PON-1 and TRAP. Leptin, sTNF-R, CCL-3 and CCL-11 were significantly higher in SCZ. There were significant associations between pro-inflammatory and O&NS biomarkers (leptin/CCL-8 and AOPP; IL-6 and NOx; CCL-3 and LOOH; CCL-3/IL-6/NOx and TRAP). In conclusion, there were significant intercorrelations between inflammatory and O&NS pathways, which play a role in the pathophysiology of chronic SCZ. O&NS markers and the enzyme PON-1 are not useful as biomarkers in chronic stable polymedicated SCZ patients.

Parkinson's Disease is Accompanied by Intertwined Alterations in Iron Metabolism and Activated Immune-inflammatory and Oxidative Stress Pathways.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by a complex interplay between peripheral and central inflammatory and oxidative stress pathways. OBJECTIVE: To investigate immune-inflammatory and oxidative stress pathways in relation to iron metabolism in peripheral blood of PD patients and healthy controls. METHOD: We recruited 56 healthy individuals and 56 PD patients in stages 1-3 of Hoehn and Yahr Scale. Plasma haptoglobin (Hp), homocysteine, interleukin 6, soluble interleukin 6 receptor, iron (Fe), ferritin, total iron binding capacity, transferrin (Tf), soluble transferrin receptor (sTfR), malondialdehyde (MDA) and paraoxonase 1 (PON1) were measured. RESULTS: PD was associated with significant changes in Tf (lowered), sTfR, ferritin, Hp, interleukin 6 and MDA (all increased) levels, while there was a trend towards a negative association with PON1. Logistic regression showed that the most significant biomarkers of PD were MDA, sTfR, Hp and ferritin. Moreover, Fe levels were negatively associated with Hp and positively with PON1, total iron binding capacity and Tf, while ferritin and sTfR were positively associated with MDA levels. CONCLUSION: Our study indicates a state of systemic inflammation and oxidative stress in PD patients coupled with alterations in Fe metabolism. Chronic inflammation and oxidative pathways in PD may in part determine changes in iron metabolism. New drug treatments for PD should target inflammatory and oxidative stress pathways and iron metabolism as well.

Conjugated linoleic acid supplementation does not maximize motor performance and abdominal and trunk fat loss induced by aerobic training in overweight women / Suplementação de ácido linoléico conjugado não maximiza o desempenho motor e a perda de gordura de tronco e abdominal induzida pelo treinamento aeróbio em mulheres com excesso de peso

ABSTRACT Objective: To analyze the effect of eight weeks of conjugated linoleic acid supplementation on physical performance, and trunk and abdominal fat in overweight women submitted to an aerobic training program. Methods: Twenty-eight overweight women (body mass index ³25 kg/m2) were divided randomly and double-blindly to receive conjugated linoleic acid or placebo, both associated with an aerobic exercise program (frequency = three times a week, duration=30 min/session, intensity=80% of maximum heart rate). Conjugated linoleic acid (3.2 g) and placebo (4.0 g) supplements were consumed daily (four capsules) for eight weeks. Maximum speed and time to exhaustion were determined in incremental treadmill test. Trunk fat was estimated by dual-energy X-Ray absorptiometry. Waist circumference was used as indicator of abdominal fat. Results: Main effect of time (p<0.05) showed increased maximum speed (conjugated linoleic acid=+6.3% vs. placebo=+7.5%) and time to exhaustion (conjugated linoleic acid=+7.1% vs. placebo=+8.6%) in the incremental treadmill test, with no differences between the groups (p>0.05). Similarly, significant reductions (p<0.05) in trunk fat (conjugated linoleic acid=-1.7% vs. placebo=-1.5%) and abdominal fat (conjugated linoleic acid=-4.7% vs. placebo=-4.0%) were found after eight weeks of intervention, with no differences between the groups (p>0.05). Conclusion: The results of this study suggest that conjugated linoleic acid supplementation does not maximize motor performance, and loss of body and abdominal fat induced by aerobic training in overweight women.

RESUMO Objetivo: Analisar o efeito de oito semanas de suplementação de ácido linoleico conjugado sobre o desempenho físico, a gordura de tronco e abdominal em mulheres com excesso de peso submetidas a um programa de treinamento aeróbio. Métodos: Vinte e oito mulheres com excesso de peso (índice de massa corporal ³ 25 kg/m2) foram separadas aleatoriamente por meio de um delineamento duplo cego para receber suplementação de ácido linoleico ou placebo associado a um programa de exercícios aeróbios (frequência = três sessões semanais, duração=30 min/sessão, intensidade=80% da frequência cardíaca máxima). A suplementação de ácido linoleico (3,2 g) ou de placebo (4,0 g) foi consumida diariamente (quatro cápsulas), durante oito semanas. As variáveis velocidade máxima atingida e tempo de permanência até a exaustão foram determinadas em teste incremental em esteira. A gordura de tronco foi estimada por absortometria radiológica de dupla energia. A circunferência de cintura foi utilizada como indicador de gordura abdominal. Resultados: Efeito principal do tempo (p<0,05) revelou aumento da velocidade máxima atingida (suplementação de ácido linoleico=+6,3% versus placebo=+7,5%) e tempo de duração até a exaustão (suplementação de ácido linoleico=+7,1% versus placebo=+8,6%) em teste incremental em esteira, sem diferenças entre os grupos (p>0,05). De forma similar, uma redução significante (p<0,05) na gordura relativa de tronco (suplementação de ácido linoleico=-1,7% versus placebo=-1,5%) e na gordura abdominal (suplementação de ácido linoleico=-4,7% versus placebo=-4,0%) foi encontrada após oito semanas de intervenção, sem diferenças entre os grupos (p>0,05). Conclusão: Os resultados do presente estudo sugerem que a suplementação de ácido linoleico não maximiza o desempenho motor e a redução da gordura de tronco e abdominal induzida pelo treinamento aeróbio em mulheres com excesso de peso.

Paraoxonase 1 (PON1) Q192R genotypes and their interaction with smoking strongly increase atherogenicity and the Framingham risk score.

OBJECTIVE: Paraoxonase 1 (PON1) polymorphisms are associated with an increased susceptibility to cardiovascular disease. PON1 Q192R polymorphism (rs662) partially determine PON1 hydrolytic activity and protect against oxidation of LDL and HDL. This study aimed to delineate the association of PON1 status (functional 192 genotype and plasma activity levels) and atherogenicity in urbans residents aged 40 years or more. MATERIALS AND METHODS: Anthropometric data, lipid profiles, the atherogenic index of the plasma (AIP) and Framingham score risk were measured. Three kinetic assays were conducted to assay PON1 status using phenylacetate and 4-(chloromethyl)phenyl acetate as substrates. RESULTS: Smoking per se did not significantly impact the AIP but the interaction PON1 genotype by smoking significantly increased the AIP. In subjects with the RR genotype smoking increased the AIP index from (estimated mean ± SEM) -0.038 ± 0.039 to 0.224 ± 0.094. The QR genotype increased the Framingham risk index by around 1.3 points. Smoking by RR genotype carriers significantly increased the Framingham risk score (17.23 ± 2.04) as compared to smoking (13.00 ± 1.06) and non-smoking (7.79 ± 0.70) by QQ+QR genotype carriers. The interaction RR genotype by smoking was a more important predictor (odds ratio = 7.90) of an increased Framingham risk score (> 20) than smoking per se (odds ratio = 2.73). The interaction smoking by RR genotype carriers significantly increased triglycerides and lowered HDL cholesterol. CONCLUSION: Smoking per se has no (AIP) or a mild (Framingham risk score) effect on atherogenicity, while the interaction smoking by PON1 RR genotype has a clinically highly significant impact on atherogenicity.

Are PTH levels related to oxidative stress and inflammation in chronic kidney disease patients on hemodialysis?

INTRODUCTION:: Patients at end stage renal disease have higher levels of inflammation and oxidative stress than the general population. Many factors contribute to these issues, and the parathyroid hormone (PTH) is also implicated. OBJECTIVE:: The study was conducted in order to assess the relationship between PTH levels and inflammation and oxidative stress in hemodialysis patients. METHODS:: Cross-sectional study with patients of two hemodialysis facilities in Londrina, Brazil. Patients with other conditions known to generate oxidative stress and inflammation were excluded. Blood levels of PTH and biochemical parameters of inflammation (interleukins 1 and 6, tumor necrosis factor-alpha) and oxidative stress (total plasma antioxidant capacity, malonic dialdehyde, lipid hydroperoxidation, advanced oxidation protein products, quantification of nitric oxide metabolites, and 8-isoprostane) were measured before a dialysis session. Then, we made correlation analyses between PTH levels - either as the continuous variable or categorized into tertiles-, and inflammatory and oxidative stress biomarkers. RESULTS:: PTH did not show any correlation with the tested inflammation and oxidative stress parameters, nor as continuous variable neither as categorical variable. CONCLUSION:: In this descriptive study, the results suggest that the inflammation and oxidative stress of hemodialysis patients probably arise from mechanisms other than secondary hyperparathyroidism. INTRODUÇÃO:: Pacientes com doença renal em estágio terminal têm níveis de inflamação e estresse oxidativo maiores do que a população geral. Muitos fatores contribuem para isso, e o hormônio paratireoidiano (PTH) é um deles. OBJETIVO:: Estudo foi realizado para avaliar a relação entre os níveis de PTH e níveis de inflamação e estresse oxidativo em pacientes em hemodiálise. MÉTODOS:: estudo transversal com pacientes de duas unidades de hemodiálise de Londrina, Brasil. Pacientes com condições causadoras de inflamação e estresse oxidativo foram exclusos. Níveis plasmáticos de PTH e parâmetros bioquímicos de inflamação (interleucina 1 e 6, fator de necrose tumoral alfa) e estresse oxidativo (capacidade antioxidante plasmática total, dialdeído malônico, hidroperoxidação lipídica, produtos avançados da degradação proteica, quantificação de metabólitos de óxido nítrico e 8-isoprostano) foram dosados antes da sessão de hemodiálise. Realizou-se análise de correlação entre os níveis de PTH - tanto como variável continua como variável categórica em tercis - e os parâmetros de inflamação e estresse oxidativo. RESULTADOS:: Não houve correlação do PTH com nenhum dos parâmetros testados, nem como variável contínua, nem como categórica. CONCLUSÃO:: Neste estudo descritivo, os resultados sugerem que a inflamação e o estresse oxidativo em pacientes em hemodiálise provavelmente tem origem em mecanismos que não incluem o hiperparatireoidismo secundário.

Paraoxonase 1 (PON1) Q192R genotypes and their interaction with smoking strongly increase atherogenicity and the Framingham risk score

ABSTRACT Objective Paraoxonase 1 (PON1) polymorphisms are associated with an increased susceptibility to cardiovascular disease. PON1 Q192R polymorphism (rs662) partially determine PON1 hydrolytic activity and protect against oxidation of LDL and HDL. This study aimed to delineate the association of PON1 status (functional 192 genotype and plasma activity levels) and atherogenicity in urbans residents aged 40 years or more. Materials and methods Anthropometric data, lipid profiles, the atherogenic index of the plasma (AIP) and Framingham score risk were measured. Three kinetic assays were conducted to assay PON1 status using phenylacetate and 4-(chloromethyl)phenyl acetate as substrates. Results Smoking per se did not significantly impact the AIP but the interaction PON1 genotype by smoking significantly increased the AIP. In subjects with the RR genotype smoking increased the AIP index from (estimated mean ± SEM) -0.038 ± 0.039 to 0.224 ± 0.094. The QR genotype increased the Framingham risk index by around 1.3 points. Smoking by RR genotype carriers significantly increased the Framingham risk score (17.23 ± 2.04) as compared to smoking (13.00 ± 1.06) and non-smoking (7.79 ± 0.70) by QQ+QR genotype carriers. The interaction RR genotype by smoking was a more important predictor (odds ratio = 7.90) of an increased Framingham risk score (> 20) than smoking per se (odds ratio = 2.73). The interaction smoking by RR genotype carriers significantly increased triglycerides and lowered HDL cholesterol. Conclusion Smoking per se has no (AIP) or a mild (Framingham risk score) effect on atherogenicity, while the interaction smoking by PON1 RR genotype has a clinically highly significant impact on atherogenicity.